eLife (Dec 2016)
Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival
- Vladimir Chubanov,
- Silvia Ferioli,
- Annika Wisnowsky,
- David G Simmons,
- Christin Leitzinger,
- Claudia Einer,
- Wenke Jonas,
- Yuriy Shymkiv,
- Harald Bartsch,
- Attila Braun,
- Banu Akdogan,
- Lorenz Mittermeier,
- Ludmila Sytik,
- Friedrich Torben,
- Vindi Jurinovic,
- Emiel PC van der Vorst,
- Christian Weber,
- Önder A Yildirim,
- Karl Sotlar,
- Annette Schürmann,
- Susanna Zierler,
- Hans Zischka,
- Alexey G Ryazanov,
- Thomas Gudermann
Affiliations
- Vladimir Chubanov
- ORCiD
- Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
- Silvia Ferioli
- Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
- Annika Wisnowsky
- Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
- David G Simmons
- ORCiD
- School of Biomedical Sciences, The University of Queensland, Brisbane, Australia
- Christin Leitzinger
- Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum Munich, Neuherberg, Germany
- Claudia Einer
- Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum Munich, Neuherberg, Germany
- Wenke Jonas
- Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany; German Center for Diabetes Research, Munich, Germany
- Yuriy Shymkiv
- Princeton Institute of Life Sciences, Princeton, United States
- Harald Bartsch
- Institute of Pathology, Ludwig Maximilian University of Munich, Munich, Germany
- Attila Braun
- Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany; Department of Vascular Medicine, University Hospital Würzburg, Würzburg, Germany
- Banu Akdogan
- Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
- Lorenz Mittermeier
- Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
- Ludmila Sytik
- Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
- Friedrich Torben
- Genome Analysis Center, Institute of Experimental Genetics, Helmholtz Zentrum Munich, Neuherberg, Germany
- Vindi Jurinovic
- Institute for Medical Informatics, Biometry and Epidemiology, Ludwig Maximilian University of Munich, Munich, Germany
- Emiel PC van der Vorst
- Institute for Cardiovascular Prevention, Ludwig Maximilian University of Munich, Munich, Germany
- Christian Weber
- Institute for Cardiovascular Prevention, Ludwig Maximilian University of Munich, Munich, Germany; German Centre for Cardiovascular Research, Munich Heart Alliance, Munich, Germany
- Önder A Yildirim
- Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum Munich, Neuherberg, Germany; German Center for Lung Research, Munich, Germany
- Karl Sotlar
- Institute of Pathology, Ludwig Maximilian University of Munich, Munich, Germany
- Annette Schürmann
- Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany; German Center for Diabetes Research, Munich, Germany
- Susanna Zierler
- ORCiD
- Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany
- Hans Zischka
- Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum Munich, Neuherberg, Germany
- Alexey G Ryazanov
- Princeton Institute of Life Sciences, Princeton, United States; Department of Cellular and Molecular Pharmacology, Rutgers Robert Wood Johnson Medical School, Piscataway, United States
- Thomas Gudermann
- Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany; German Centre for Cardiovascular Research, Munich Heart Alliance, Munich, Germany; Comprehensive Pneumology Center Munich, German Center for Lung Research, Munich, Germany
- DOI
- https://doi.org/10.7554/eLife.20914
- Journal volume & issue
-
Vol. 5
Abstract
Mg2+ regulates many physiological processes and signalling pathways. However, little is known about the mechanisms underlying the organismal balance of Mg2+. Capitalizing on a set of newly generated mouse models, we provide an integrated mechanistic model of the regulation of organismal Mg2+ balance during prenatal development and in adult mice by the ion channel TRPM6. We show that TRPM6 activity in the placenta and yolk sac is essential for embryonic development. In adult mice, TRPM6 is required in the intestine to maintain organismal Mg2+ balance, but is dispensable in the kidney. Trpm6 inactivation in adult mice leads to a shortened lifespan, growth deficit and metabolic alterations indicative of impaired energy balance. Dietary Mg2+ supplementation not only rescues all phenotypes displayed by Trpm6-deficient adult mice, but also may extend the lifespan of wildtype mice. Hence, maintenance of organismal Mg2+ balance by TRPM6 is crucial for prenatal development and survival to adulthood.
Keywords
